The National Health & Medical Research Council (NHMRC) has provided $606,000 to SRI affiliated scientists for the study ‘The Effectiveness of Cognitive Behaviour Therapy for Young People at Risk of Serious Mental Disorders’.

It has long been known that schizophrenia onset is usually preceded by an often lengthy ‘prodrome’ period of steadily worsening symptoms, and several studies have investigated the efficacy of ‘early intervention’ strategies to prevent onset during this period.

Using the current ‘At Risk Mental States’ (ARMS) criteria to assess individual risk has successfully predicted onset in 40-50 percent of assessed cases. That is, around half of all
young people tested and considered to be at risk did indeed develop psychosis within 6-12 months after assessment. It is this demonstrated ability to identify those at risk which has made preventative treatment a realistic proposition.

Early intervention treatment with Cognitive Behaviour Therapy (CBT) and low doses of antipsychotic medication has been relatively successful in interrupting the decline into psychosis and improving overall outcomes, but it remains unclear what proportion of such successes are due to CBT ‘counselling’ or to medication. The new study will treat a cohort of young people
at risk solely with a course of CBT formulated especially for psychosis prevention. If the effectiveness of treating with CBT alone is comparable to that of CBT + low dose medication, the treatment could negate the ethical difficulties of prescribing antipsychotics to young people who prove not to be at risk, and become viable for wide application as an early intervention therapy.

Mental Health in Rural Areas

The NHMRC has also provided $718,000 for the study ‘Mental Health and Well Being in Rural and Remote NSW’. The largest investigation of its kind yet undertaken, This multicentre
study will be administered from four locations in rural NSW (Orange, Broken Hill, Moree and Lismore) representing the bases of the four collaborating rural research units, and will be coordinated from the Centre for Rural and Remote Mental Health, in Orange.

This unique rural Australian study will investigate individual, family and community factors associated with the mental health and wellbeing of rural communities.

After completing his SRI-supported PhD thesis ‘Sleights of mind: delusions and self-deception’ at Macquarie University last May, Ryan McKay was offered a position at the National Hospital for Neurology and Neurosurgery in London. In September, however, Dr McKay took up a Research Associate position at Boston’s Tufts University Centre for Cognitive Studies, which is headed by one of the world’s most influential contemporary philosophers of mind, Prof. Daniel Dennett.

Completed at the Macquarie Centre for Cognitive Science, Dr McKay’s study* investigated the motivation underlying persecutory delusions using a new instrument of measurement, the ‘Paranoid, Persecutory and Delusion-Proneness Questionnaire’. His results to date have brought to light the self-defensive motivation of some delusional beliefs.

Medical opinion remains divided as to the cause of paranoid and delusionary beliefs in schizophrenia. To what degree are they due to a self-defensive need to ‘blame’ undesirable events on delusory causes or, alternatively, to biologically malfunctioning brain cells?

Individuals with persecutory delusions may be protecting their self-esteem by projecting their negative self-representations onto others. The cost of maintaining self-esteem in this way, however, is that such people must live in a delusional world populated by hostile, malevolent beings. A key motivation for such beliefs may also be the need to explain why the life events and social disruptions caused by the mental illness are happening. If the individual continues to deny the reality of their mental illness, such delusions are the means which enable them to maintain denial.

As every family member coping with a delusional relative knows, it is often impossible to convince individuals that their distorted interpretations of events are due to their illness. The human mind usually prefers to believe any other explanation, rather than the explanation that it is mentally ill.

Dr McKay’s research is valuable for the ongoing development of a balanced therapy for psychosis, particularly as a component of the Cognitive Behaviour therapy which is applied
with medication as standard treatment.

Many studies have confirmed that schizophrenia causes reductions in the grey matter of the brain, but few have investigated which brain areas are most affected and whether these areas relate to the symptoms of the illness.

A SRI-supported study* led by Tom Whitford at the Brain Dynamics Centre, Westmead Hospital,
has used MRI to compare the brain structures of 31 male and female patients with 30 healthy control subjects. All participants were around the age of 19 years, and all patients were recruited to the study within 3 months of being diagnosed with first episode schizophrenia – therefore medication effects were minimal. To further rule out any brain abnormalities not due to schizophrenia, subjects with any history of brain injury, drug abuse, or mental retardation were
excluded.

The aim of the study was to identify regions of grey matter reduction, and to test whether
the severity of such reductions corresponded with the type and severity of patients’ symptoms.

Each patient was assessed using established tests to measure the three basic syndromes of
schizophrenia: Psychomotor Poverty (inertia of thought), Disorganisation (disordered thinking), and Reality Distortion (delusions, hallucinations). The research team predicted that Psychomotor Poverty and Disorganisation would be associated with grey matter reductions in the prefrontal cortex, while Reality Distortion would be associated with such reductions in the temporal regions.

The results confirmed the findings of other studies that there was an overall deficit of grey matter in the brains of young people experiencing first episode schizophrenia, and also identified four distinct regions of such reduction (see illustrations). However, the research team found significant correspondance between degrees of grey matter reduction and severity of symptom only in the case of Reality Distortion. It was found that patients assessed with more severe Reality Distortion symptoms had correspondingly less grey matter deficit than other
patients in three of the four brain areas identified.

A New Model of Schizophrenia Is sensory deprivation during brain development the single cause?

Schizophrenia is now considered to be a neurodevelopmental disorder with origins in the
prenatal or neonatal period. The variety of symptoms which appear in later life are considered to be the end results of a cascade of effects possibly dating back to a single original abnormality.

The brains of people with schizophrenia have enlarged ventricles, reduced cortical thickness,
increased neuronal density in the prefrontal cortex, and differences in other brain areas. Establishing the fact of these differences has occupied much of neuroscience research for the last decade, and the results of these earlier investigations have equipped researchers to now seek the cause or causes of them.

Along with brain structural and functional abnormalities, schizophrenia is also characterised
by reduced pain sensitivity and reduced niacin (vitamin B3) skin flare reaction. Following this ‘clue’, a SRI/University of Newcastle team proposed that the cascade of schizophrenia effects may originate with a chronic neurodevelopmental deficit in the sensory neurons. These ‘afferent’ neurons send information from our sensory receptors (e.g., skin, eyes, nose, tongue, ears ) toward the central nervous system and the brain. They are some of the largest neurons in the
body, some extending to 40 cms in length, and are responsible for triggering our senses including touch, temperature and pain, and for our sense of posture, movement and facial expression. The Newcastle team’s hypothesis was that original deficits in the afferent neuronal
system could starve the infant brain of the continual flow of sensory information needed for normal development.

To test this, the team employed a number of male and female newborn rats, and used injections
of capsaicin under anaesthetic to produce significant permanent loss of afferent neurons in half the group, thus subjecting their developing brains to a degree of continual sensory deprivation.
Then the behavioural differences of both groups were observed during 40 days of development, before both the treated and untreated groups were euthanised and differences in brain structure examined.

Remarkable Similarities

The biological effects of the induced sensory deprivation on the treated rat brains, and
their parallels with abnormalities found in human schizophrenia brains were remarkable.

Compared to the untreated rats, the brain weights of the treated male rats were significantly
lower, but the female treated rat brains were the same weight as that of the untreated females.

The cortices of both male and female treated rats were thinner than normal – as found
in schizophrenia.

The ventricles of the treated rats were significantly larger than those of untreated rats,
and their hippocampus areas and corpus callosums were smaller. Similar abnormalities are found in schizophrenia.

Increased neuronal density in many brain areas was observed in male and female treated
rats. This is reflected in similar densities in schizophrenia.

Overall, the male treated rats were affected more severely than the females, and this
aligns with the preponderance of males affected by schizophrenia.

The development of the visual cortex was unaffected in the treated rats. This brain
area is unaffected by schizophrenia.

A New Direction for Research

Recent studies have added to the evidence that schizophrenia causes a reduction in cortex
volume, and a 10 – 17 percent increase in density of brain cells – probably due to reduction of the ‘neuropil’ material (synaptic elements and neuronal connections) between cells. This loss of cellular connectivity could underlie abnormalities of information processing and produce the cognitive dysfunctions of the illness.

Building on this, the Newcastle study results support the adoption of a promising new model for the cause of schizophrenia, and suggest that the illness results from an intrinsic somatosensory deprivation that causes subnormal proliferation of brain cell connectivity during the brain’s development.

This deficit remains undetected until the normal process of synaptic ‘pruning’ in adolescence
further reduces connectivity to a level below the threshold required for normal processing – resulting in the gradual onset of schizophrenia symptoms.

As well as demonstrating for the first time the importance of the somatosensory nervous system
to brain development, the study has signposted a valuable new direction for schizophrenia research.

Whose Brain is it, Anyway?The NSW Tissue Resource Centre investigates the barriers to brain donation – and
breaks through them

In April last year the Australian laws applying to transplant organ donation were changed to allow a registered donor’s organs to be collected without first obtaining permission from relatives. This
important amendment assigns first priority to the donor’s wishes, and is expected to significantly reduce the number of people who die while waiting for transplants – currently around 150 deaths
per year.

Under current regulations, however, a distinction is made between donation of organs for transplantation and donation for research. Unlike other organs the brain is not
included in the ‘list’ that is available via the drivers license system or with the Australian Organ Donor Register. These regulations severely handicap mental illness researchers – and at a time when new technology is available to gain maximum research value from the donated brain tissue.

In 1995 the transplant donor rate in Australia was 10.3 donors per million of population, half the rate of the United States. This poor performance is at odds with current opinion polls, which report that around 90 per cent of Australians approve of organ donation. The discrepancy
between such public opinion and actual numbers of organs donated can only be due to the bureaucratic complexity which must be unravelled before collection is permitted. And in the case of the brain, Tissue Resource Centre staff have only 48 hours after death to complete collection before the organ deteriorates and may not be useful for research purposes.

In a recent SRI-supported study* Therese Garrick and colleagues have investigated the views
of 180 registrants on the ‘Using Our Brains’ donor program, which shares the NSW Tissue Resource Centre with SRI’s ‘Gift of Hope’ brain donor program. Around 90 percent of the total group believed that their brains would be collected after death because they had signed the donor section of their licences or had completed donor cards. This is not the case, but is a belief held by most of the population. Most participants reported that they had decided to become a brain donor because they knew someone with a brain disease or disorder and wanted to help advance medical research. Importantly, although all donors had discussed the desire to be a brain donor with their next-of-kin, the donors believed that they shouldn’t have to gain ‘permission’ from their next-of-kin.

Also significantly, 78 percent of registrants were members of transplant organ donor programs, as well as members of the ‘Using Our Brains’ research-based program. This indicates that the current legal distinction between the two is redundant, and that most donors are not concerned whether their organs are used for research or transplantation.

These findings suggest that the complex logistic and bureaucratic processes required for organ donation to research are contrary to donors’ opinions or wishes, and severely handicap Australian mental health research. It is hoped that the publication of the study will help to redress the current inequity.

The Power of Human Contact

In a second study**, SRI’s Lisa Azizi and colleagues investigated the responses of families to the request for brain tissue donation for research. Previous research on organ donation for transplantation indicated that in NSW, refusal by families for transplant donation occurred
in 56 per cent of cases in 1995, and had risen to 82 percent in 1999. Despite these figures, public opinion polls show that 90 percent of Australians are in favour of organ donation in principle. The only way to account for this discrepancy is by examining the methods
whereby next of kin are provided with the opportunity to donate organs and tissues.

Earlier studies had shown that when organ coordinators were able to meet with relatives to discuss the transplant donation issue, consent was granted in 71 percent of cases, and that permissions were also readily obtained when relatives were contacted by phone. The key element seemed to be that next-of-kin needed to discuss the matter sympathetically and to have their questions answered, which was more successfully achieved by telephone or face-to-face interviews than by less personal methods such as written letters.

These findings all related to transplant donors, so Lisa Azizi and Therese Garrick set out to discover if similar results could be obtained for brain donations for research. Hitherto, telephone approaches were considered to be intolerable intrusions on grieving families. It was also believed
that requests for brain donation in particular would cause offence and receive negative responses since the brain, like the heart and eyes, is considered one of the defining organs for an individual. These perceptions proved inaccurate.

Of the 48 families contacted by phone over 12 months, 58 percent gave permission for the brain tissue to be collected for research. Most of the families that preferred not to donate explained that they did so only because they knew the deceased’s wishes on the matter. No families were
upset or offended by being contacted on the day of the autopsy, and all were interested in the details and potential of the research proposed. It was unanimously agreed upon by families that the option to donate brain tissue for research should be spread more widely.

The research team was overwhelmed by this response, which ran against all public perception.
The majority of permitting families commented that the phone call and their decision had a positive effect on their emotional condition. The thought that the deceased would make such a valuable contribution was felt as a comfort in a time of sadness.

SRI’s Newcastle team combines two research techniques to investigate how schizophrenia affects recognition of emotion.

For family members one of the most upsetting characteristics of schizohrenia is how it sometimes changes a normally responsive and empathetic person into what seems to be a detached stranger. No matter how hard the family tries to convey its concern, the affected member seems not to care, or to be incapable of recognising the anxiety and disruption his/her behaviour is causing.

Earlier studies of facial emotion recognition in schizophrenia have indicated that patients scored very poorly at recognising negative facial expressions such as fear, disgust and anger, but scored close to normal at recognising happy expressions. Opinion among scientists about how this happens is divided: some say it may be due to a conscious decision to avoid acknowledging
negative responses, others suggest it may be due to abnormal processing in brain regions specifically responsible for recognising negative emotions.

Investigating the latter hypothesis, some studies have linked this negative emotion recognition abnormality to dysfunction of the brain’s limbic structures, which emotionally ‘colour’ all received impressions. This limbic system includes the amygdala, and is what accounts for the fact that we do not choose what to feel before we feel it.

The limbic system assigns emotional content to all incoming impressions independently and informs the cognitive frontal lobes. During emotional confrontations, for example, we all observe what is happening immediately in terms of cold information, and feel the emotional impact of it shortly after, as interpreted by the limbic system. The process takes from a fifth to a half second.

In a new study*, SRI scientist Pat Johnston and colleagues at the University of Newcastle have combined the latest fMRI brain scanning methods with Event-Related-Potentials (ERPs – measurements of the brain’s electrical activity collected via electrodes placed on the scalp) to explore how schizophrenia affects the brain’s processing of emotions. The combination of the
two techniques allowed the team to investigate when (with ERPs) and where (with fMRI) deficits in facial expression recognition and emotion processing occur.

Composite ERP brainwave activity recordings of normal controls (CON) and schizophrenia subjects (SCZ) while performing
a facial emotion recognition task. Of particular significance is that schizo-phrenia subjects less accurately discriminate between
emotion expressions at a very early stage of information processing.

ERPs were collected from 11 schizophrenia patients and 15 controls. fMRI scans were obtained from 10 patients and 10 controls. All research subjects were asked to perform the same two
tasks. First, each was shown a series of 56 photos of male and female faces displaying different emotions (happiness, fear, anger, etc.) and asked to simply count the numbers of male and female faces. The ERP and fMRI records of each subject’s brain activity during this ‘attention to gender’ performance were used to highlight any differences recorded in the second task, which was about emotion recognition. In this ‘attention to expression’ task, all subjects were shown the same series of faces and asked to count the number of faces showing surprise. In order to do this, they had to assess the emotional content of all 56 face images while the ERPs or fMRI
recorded their brain activity.

A. Composite fMRI scans of all normal control subjects’ brains (at five different levels) while they completed a facial
emotion recognition task. The red colour shows areas of special activation. B. Composite Images of all schizophrenia subjects performing the same task. C. Significant areas of different activation are revealed to be in the fusiform gyrus (Fg), middle temporal gyrus (MTg), amygdala (Amg), inferior frontal gyrus (IFg) and middle occipital gyrus (MOg).

Compared to the control subjects, schizophrenia subjects showed reduced fMRI activity in the fusiform and superior temporal gyri, a brain area known to be involved in the earliest stage of the facial recognition process. The ERP results supported this finding by showing a distortion at the beginning of the vertex positive potential, the electrical waveform associated with facial recognition. Importantly, these abnormalities were evident whether the schizophrenia subjects were recognising gender differences or expression differences.

These results indicate that schizophrenia disrupts the brain’s facial perception processes at the very earliest ‘encoding’ stage, before the more elaborate emotion recognition mechanisms of the limbic system are activated.

Further research is needed to investigate whether this disruption is indeed the root source of the emotional alienation observed in schizophrenia.

The SRI Virtual Brain Bank has been awarded a $95,000 grant from the Australian Research
Council (ARC)* to help the initiative expand into the world’s biggest online collaborative mental health research facility.

The Virtual Brain Bank is a growing database of three-dimensional digital images of brains, currently of 250 schizophrenia patients and normal control subjects. These images are held at four separate locations: the Centre for Mental Health Studies, and the School of Behavioural Sciences at University of Newcastle; the Schizophrenia Research Unit at Liverpool Hospital, and the Laboratory of Neuro Imaging at University of California Los Angeles.

SRI’s Paul Rasser pioneered the introduction into Australia of UCLA’s ‘Brain Atlasing’ imaging technique which allows differences in anatomy between brains to be accurately compared. The images above show one of the brains on the ‘Virtual Brain Bank’ at two stages of its full 3D rotation.

It was always intended that the Virtual Brain Bank would link to the Schizophrenia Research Register and to the DNA Bank to offer an unrivalled source of data to worldwide researchers. The ARC funding will fast track this plan with massive mobilisations of hardware and software, creating an online global centre of integrated mental health research collaborations.

This SRI innovation has arisen in response to the new understanding within the neuroscientific
community that the complexities of mental illness will only be unravelled by allowing cross-pollination of data from such diverse research fields as neuroimaging, neurobiology, cognitive neuroscience, clinical studies and genetics. Each field is now highly complex and specialised,
so the need is for large-scale collaborative programs spanning multiple laboratories and mobilising many types of expertise.

It is hoped that the expanded Virtual Brain Bank will eventually provide the information and the venue for such collaborations to take place.

Essential fatty acids play an important role in neural membrane structure and function, influencing the activity of a range of neural chemical signalling systems in the brain.

These polyunsaturated fatty acids are divided up into the two families of omega- 6 (found in cereals, eggs, poultry, most vegetable oils, whole-grain breads, baked goods, and margarine)
and omega-3 (found in oily cold-water fish and fresh seaweed). Abnormally low levels of both types are associated with schizophrenia.

Fatty acids, stress and cannabis

A preliminary study led by Sharon Monterrubio at Wollongong has investigated the relationship between fatty acids, cannabis use and stress in schizophrenia. This line of research was inspired by evidence that cerebrospinal fluid levels of anandamide (a neurotransmitter formed from an omega-6 fatty acid) were abnormally high in patients with schizophrenia. Anandamide is known to affect the stress-regulating cannabinoid system, and higher levels are associated with reduced symptoms.

In addition, cannabinoid (CB1) receptor levels have been found to be elevated in post-mortem brains from patients. In this context, the possible relationship between fatty acid levels, anandamide levels, alterations in stress mechanisms and cannabis use by individuals with schizophrenia was investigated.

Fatty acid levels were measured in red blood cell membranes of 12 clozapinemedicated patients. Six had never used cannabis, and six had stopped using cannabis more than six months prior to the study. Stress levels were also measured using standardised questionnaires.

The study found that high levels of arachidonic acid and other fatty acids that enhance anandamide function were associated with lower levels of nervous tension-stress, but only
in the former cannabis users.

At the same time, high levels of linoleic acid, a fatty acid that is abundant in diet, were strongly associated with higher levels of nervous tension-stress – again, only in former cannabis users.

These results suggest that fatty acids may aid cannabis-using individuals with schizophrenia to cope with stress. While promising from the point of view of developing pharmacological and/or dietary interventions which may help protect stabilised patients from relapse, further research with larger numbers is needed.

How fats affect rats

In another Wollongong study**, Teresa du Bois and colleagues have been looking at the influence of different fat diets in rats: focusing on how different levels of fat consumption
affect muscarinic acetylcholine receptor binding levels, which are involved in normal cognition, mood and motor functioning.

Rats were fed on either a saturated fat, omega-6 polyunsaturated fat, omega-3 polyunsaturated fat or low fat diet. Examination of the post-mortem brains showed that, compared to the low fat intake group, only the group fed omega-6 polyunsaturated fats showed a reduction in the density of acetylcholine muscarinic receptors.

These results suggest that a diet high in omega-6 polyunsaturated fatty acids may selectively alter neurotransmission activity in rat brains. Similar effects in humans have yet to be investigated.

In 2002, Dr Katerina Zavitsanou and colleagues in SRI’s University of Wollongong centre published their findings of increased levels of glutamate neurotransmitters in the anterior
cingulate cortex (ACC) of schizophrenia-affected brains. As glutamate is the primary trigger of excitatory brain activity, and the ACC plays a fundamental role in cognition and attention, these findings were a highly significant addition to the growing body of evidence that such abnormal excitatory activity in the ACC played a key role in schizophrenia.

SRI’s Beta-Imager at the University of Wollongong reveals a 40% increase of glutamate NMDA neuroreceptors in the PCC of schizophrenia brain tissue (left) as compared with tissue from healthy donors (right).

Dysfunction in the ACC has been directly linked to disorders such as obsessive-compulsive and bipolar, as well as to depression, autism and schizophrenia. All evidence indicates this brain area as a key “accident black spot” in the brain’s busy pathways.

Led by SRI scholar Kelly Newell, a further study* at Wollongong has explored whether the abnormal glutamate activity found in the ACC is also present in the posterior cingulate
cortex (PCC). The PCC tissue from schizophrenia and control subjects was examined for the binding of three kinds of glutamate receptors; NMDA, AMPA and kainate.

The results showed no difference in AMPA or kainate, but a highly significant 40 percent increase in NMDA neuroreceptors in the schizophrenia brain tissue.

This is the first time a selective increase in NMDA receptors has been demonstrated in the posterior cingulate cortex in schizophrenia.

Together with the earlier ACC study, this evidence of increased glutamate densities in two regions of the cingulate cortex strongly indicates a source of dysfunction that could alter
activity in related brain circuits and result in abnormal information processing.

The St. George Foundation has added a further $10,000 to the $75,000 provided for the St.George Foundation Schizophrenia Research Scholarship – which has funded Kelly Newell’s research.

The Windows of the Soul How does schizophrenia affect the ability to share attention and empathy?

For some families caring for a schizophrenia-affected relative, one of the most disturbing behavioural effects is the emotional ‘blunting’ or lack of empathy shown by many patients. Some parents, for instance, refer to the “glass wall” that has appeared between themselves and their son or daughter after onset. Neuroscience refers to this category of empathetic interpersonal abilities as ‘social cognition’, and asserts that it is severely impaired by schizophrenia.

Ongoing SRI studies at the University of Newcastle have revealed that schizophrenia
subjects and their family members exhibit abnormal eye scanpaths when viewing emotionally expressive face images, and have suggested that such scanpath anomalies could be linked to deficits in social cognition. And at the Macquarie Centre for Cognitive Science, a SRI affiliated team is investigating the remedial effects of training people to deliberately correct these scanpath abnormalities.

Now, Dr Robyn Langdon and collaborators at the Macquarie Centre for Cognitive Science
have completed two studies* further investigating social cognitive deficits in schizophrenia.

The Eye of the Beholder

Dr Langdon’s first study was based on the hypothesis that schizophrenia’s social cognitive
deficits may be associated with a reduced ability to share attention with others, and that this deficit may be measured by testing the automatic reflex of detecting and following another person’s change in direction of gaze. Though simple, this reflex is a fundamental indicator of shared attention.

The experiment involved 30 subjects with schizophrenia and 24 healthy controls. The test apparatus was a series of pictures flashed on a computer screen of a female head which looked either right or left, before a ‘target’ red star appeared in one of the empty boxes shown in each side. The interval between the head turning right/left and the appearance of the target was varied from 100 to 800 milliseconds.

Subjects were asked to simply click the space bar on the keyboard as soon as possible
after seeing the target star. By varying the head turn direction, the speed of change in the sequence of images, and recording the speed of space bar clicks, the research team was able to assess how much each subject was distracted by the gaze direction of the central head.

Subject’s ‘scores’ were then processed to arrive at a measure of the gaze direction
sensitivity of each group.

Summarising her results, Dr Langdon reports that, contrary to expectations, the schizophrenia
subjects were abnormally over-responsive to the gaze direction of the image, not under-responsive as predicted.

This surprising result suggests that the emotional blunting and unresponsiveness observed
in schizophrenia may not be due to deficits in attention sharing, but rather to deficits in interpreting the intention of interpersonal ‘signals’ received from others.

Feeling What Others Feel

Dr Langdon’s second study was devised to investigate the degree to which schizophrenia
causes misinterpretation of the intentions or emotional states of others.

Empathy has been described as the ability to feel an emotional response, which is more appropriate to someone else’s situation than to one’s own: that is, to ‘put yourself in another’s shoes’. Dr Langdon’s method of measuring this ability was to use cartoons of simple emotional situations; to blank out the facial expressions of the characters involved, and to ask study subjects to choose which facial expressions matched each frame of the cartoon.

One of the picture puzzles used to measure research subjects? ability to interpret the emotional content of social interactions.
Subjects were asked to assign a pair of facial expressions (A, B or C) to each frame of the cartoon strip above. The correct sequence is C, A, B.

After comparing the results of 22 schizophrenia-affected subjects and 18 healthy controls,
it was found that schizophrenia subjects scored significantly lower than controls in choosing correct facial expressions, and that the lowest scores were recorded by those with the longest duration of illness.

This study provides the first direct empirical evidence that schizophrenia impairs the
ability to attribute emotions appropriately on the basis of how another person is likely to be feeling in specific circumstances.